Metabolism of Natural Killer Cells and Other Innate Lymphoid Cells

Cong, Jingjing

doi:10.3389/fimmu.2020.01989

Cited by 46 publications

(35 citation statements)

References 147 publications

(237 reference statements)

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“…NK cells are innate lymphocytes with a dominant role in the early defense against tumors and intracellular pathogens, and their dysfunction leads to added susceptibility to virus infections. The acquisition of full effector function in NK cells require substantial metabolic reprogramming (2,3). Recent research has defined enhanced cellular metabolism in lymphocytes, including NK cells, as indicative of immune responsiveness, while impaired metabolism resulted in immune cell dysfunction and compromised immunity.…”

Section: Discussionmentioning

confidence: 99%

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Expression of Nutrient Transporters on NK Cells During Murine Cytomegalovirus Infection Is MyD88-Dependent

et al. 2021

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Natural killer (NK) cells are the predominant innate lymphocytes that provide early defense against infections. In the inflammatory milieu, NK cells modify their metabolism to support high energy demands required for their proliferation, activation, and functional plasticity. This metabolic reprogramming is usually accompanied by the upregulation of nutrient transporter expression on the cell surface, leading to increased nutrient uptake required for intense proliferation. The interleukin-1 family members of inflammatory cytokines are critical in activating NK cells during infection; however, their underlying mechanism in NK cell metabolism is not fully elucidated. Previously, we have shown that IL-18 upregulates the expression of solute carrier transmembrane proteins and thereby induces a robust metabolic boost in NK cells. Unexpectedly, we found that IL-18 signaling is dispensable during viral infection in vivo, while the upregulation of nutrient transporters is primarily MyD88-dependent. NK cells from Myd88-/- mice displayed significantly reduced surface expression of nutrient receptors and mTOR activity during MCMV infection. We also identified that IL-33, another cytokine employing MyD88 signaling, induces the expression of nutrient transporters but requires a pre-exposure to IL-12. Moreover, signaling through the NK cell activating receptor, Ly49H, can also promote the expression of nutrient transporters. Collectively, our findings revealed multiple pathways that can induce the expression of nutrient transporters on NK cells while highlighting the imperative role of MyD88 in NK cell metabolism during infection.

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Section: Discussionmentioning

confidence: 99%

“…Natural killer (NK) cells are predominant effector lymphocytes involved in anti-tumor and antiviral immune responses and provide the first line of defense without prior sensitization (1,2). The role of NK cell metabolism in facilitating robust effector functions is emerging as a key aspect in recent studies (3,4).…”

Section: Introductionmentioning

confidence: 99%

Expression of Nutrient Transporters on NK Cells During Murine Cytomegalovirus Infection Is MyD88-Dependent

et al. 2021

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“…Although traditionally classified as innate cells, they also have important functions in aiding the adaptive response. Increased energy requirements to properly kill tumor and virus-infected cells require a metabolic switch from OXPHOS to glycolysis ( 94 ).…”

Section: Acly In the Innate Immune Systemmentioning

confidence: 99%

Exploring the Role of ATP-Citrate Lyase in the Immune System

2021

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Studies over the past decade have revealed that metabolism profoundly influences immune responses. In particular, metabolism causes epigenetic regulation of gene expression, as a growing number of metabolic intermediates are substrates for histone post-translational modifications altering chromatin structure. One of these substrates is acetyl-coenzyme A (CoA), which donates an acetyl group for histone acetylation. Cytosolic acetyl-CoA is also a critical substrate for de novo synthesis of fatty acids and sterols necessary for rapid cellular growth. One of the main enzymes catalyzing cytosolic acetyl-CoA formation is ATP-citrate lyase (ACLY). In addition to its classical function in the provision of acetyl-CoA for de novo lipogenesis, ACLY contributes to epigenetic regulation through histone acetylation, which is increasingly appreciated. In this review we explore the current knowledge of ACLY and acetyl-CoA in mediating innate and adaptive immune responses. We focus on the role of ACLY in supporting de novo lipogenesis in immune cells as well as on its impact on epigenetic alterations. Moreover, we summarize alternative sources of acetyl-CoA and their contribution to metabolic and epigenetic regulation in cells of the immune system.

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“…It should be noted that defining a metabolic pathway for the NK cells is a step towards identifying a therapeutic target that addresses this pathway and specifically activates the cytotoxic activity of the NK cells. Production of certain metabolites limits the survival and function of NK cells, including pyruvate dehydrogenase kinase 1, lactate dehydrogenase A (LDHA), and adenosine (ADO) [ 93 ]. Interestingly, lipid-lowering drugs represent a potential therapy for patients with ER-positive breast cancer.…”

Section: Natural Killer Cell-mediated Immunotherapeutics In Breast Cancermentioning

confidence: 99%

Natural Killer Cell Dysfunction in Obese Patients with Breast Cancer: A Review of a Triad and Its Implications

Elaraby

Malek

Abdullah

et al. 2021

Journal of Immunology Research

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Natural killer cells (NK cells) are a crucial constituent of the innate immune system as they mediate immunity against viruses, bacteria, parasites, and most importantly, tumor cells. The exact mechanism of how the innate immune system and specifically NK cells interact with cancer cells is complex and is yet to be understood. Several factors that constitute the tumor microenvironment (TME) such as hypoxia and TGF-β are believed to play a role in the complex physiological reaction of NK cells to tumor cells. On the other hand, several risk factors are implicated in the development and progression of breast cancer, most importantly: obesity. Cytokines released from adipose tissue such as adipokines, leptin, and resistin, among others, are also believed to facilitate tumor progression. In this study, we aimed to build a triad of breast cancer, obesity, and NK cell dysfunction to elucidate a link between these pillars on a cellular level. Directing efforts towards solidifying the link between these factors will help in designing a targeted immunotherapy with a low side-effect profile that can revolutionize breast cancer treatment and improve survival in obese patients.

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Metabolism of Natural Killer Cells and Other Innate Lymphoid Cells

Cited by 46 publications

References 147 publications

Expression of Nutrient Transporters on NK Cells During Murine Cytomegalovirus Infection Is MyD88-Dependent

Expression of Nutrient Transporters on NK Cells During Murine Cytomegalovirus Infection Is MyD88-Dependent

Exploring the Role of ATP-Citrate Lyase in the Immune System

Natural Killer Cell Dysfunction in Obese Patients with Breast Cancer: A Review of a Triad and Its Implications

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